I mentioned I had a full schedule last week that, among other things, wouldn't permit me to watch the ACIP meetings live. What was not on my schedule was an acute illness, now well on the mend but leaving me both very fatigued and even further behind on my other duties than planned. From my brief scan of the ACIP presentation slides and the buzz in the news and medical communities, I'm sure if I had watched it live I'd have been in intensive care by now.
I'll eventually watch the sessions recordings, which aren't yet posted as of Sunday morning. Before my illness I had planned to discuss other issues this week, but instead I'll just mention those items briefly and provide you with links if you want to explore further.
CDC Weighs in on Ebola in the DRC
Last Thursday CDC sent out an official warning about Ebola on its Health Alert Network. Nothing significant to add to when I posted about the outbreak on September 7 - we can expect to learn about more cases for a while, then hope to see things come under control.
New FDA VRBPAC Meeting October 9
This was just announced, but unlikely to be too controversial. The agenda contains only 2 items: recommendations for flu vaccine strain composition for the 2026 southern hemisphere flu season and a discussion of an allergen standardization program.
Johns Hopkins County-Level Measles Surveillance
I had been looking at this site recently and mentioned it in a recent post. JHU has put together something similar to their covid dashboard they provided during the pandemic; that site was really useful and widely used by both scientific groups and lay press. As we have seen all too clearly this year, it only takes pockets of unimmunized people to set off a large measles outbreak. State-wide immunization levels don't really tell us much about this. County-level data should be about the largest sample size we look at to understand measles outbreak risks.
The JHU team provided more details about its platform in a new article last week. I'll be keeping an eye on this dashboard. Here's the past 2 weeks numbers, almost all represent local transmission.
FAERS
Not a typo. You know about VAERS where anyone can report an adverse event they think was related to a vaccination. It has long been misused by anti-vaccine groups who either don't understand the system or just want to use it to manipulate vaccine fear.
FAERS is the FDA Adverse Events Reporting System, sort of the equivalent of VAERS but for drugs. Now one of my go-to journal watch systems, Retraction Watch, sounds an alarm about misuse of FAERS primarily to funnel into paper mills. Be wary of any publication using FAERS data. This figure from a preprint article shows the potential scope.
Better Luck Next Week
Sorry for the brevity of today's post, I hope to be back full strength next week!
Or haze, or just blackness. It's a beautiful sunny day in Maryland, but cancellation of the FDA's VRBAC meeting to discuss next fall's flu vaccine composition makes things a lot hazier. More on that later.
Covid Vaccination Protective Against Post-Covid Conditions in Children
This is a report from a multicenter study of children 5-17 years of age, originally enrolled July 2021-September 2022 and then followed longitudinally. The cohort was surveyed from December 2022 through May 2023, with questions about a variety of symptoms lumped under Post-Covid Conditions (PCC) detailed in the footnotes below.
The lower odds ratios of PCC in vaccinated children is impressive. The study's strengths are its prospective design, but the fact that they are relying on survey results, as opposed to specific follow-up encounters to determine signs and symptoms, is a bit of a weakness. Other longitudinal studies are ongoing with longitudinal in-person evaluations, so we'll eventually have better data. Also, this study doesn't tell us anything about benefits of ongoing covid immunizations in children. I've previously mentioned other studies suggesting benefit to children from ongoing immunizations.
Measles
The outbreak in Texas with probable spillover to New Mexico continues. Here's the latest from CDC in their February 28 report. Be aware there is a time lag from when cases are reported by states to when they are included in CDC numbers.
I was hoping the West Texas outbreak wouldn't result in large numbers of cases given the relatively rural and smallish population involved; we aren't yet approaching the 2019 New York outbreak that occurred in a densely populated community.
The Texas authorities' update from Friday tallies 146 cases, and New Mexico shows 9 cases. Five of the NM cases were 18+ years of age and 4 children 5-17 years old. Texas HHS also reports a large exposure area for a measles case in San Antonio and surrounding area. I think it's interesting to look at the sites and consider the immense resources needed to track down and protect exposed people.
WHO Soldiers On
The polio vaccination program in Gaza sounds like it was very successful: 603,000 children under 10 years of age were immunized over a 5-day period, aided by the cease-fire that I hope will continue.
New World Screwworm
Apologies, I think I've mentioned this topic once before but can't find it in a search of my posts. This disease is a form of myiasis, and the recent news is that it's getting closer to the US with new data at the end of last year showing the fly (Cochliomyia hominivorax) appeared in Mexico. The previous "barrier" to creeping closer to the US was the Darrien Pass in Panama, which you may recall from various immigration discussions in the lay press.
Now new efforts are underway to release sterile flies in Mexico, an established method to control the population. The USDA has a helpful document explaining the history. In endemic countries this is mostly a concern for livestock and other animals, but we humans also can be affected; it is very painful, beyond unpleasant, and gross, requiring manual extraction of the fly larvae from soft tissue. Here's the history in the US, at least as of late 2016 following the finding of the flies in Florida, resulting in a sterilized fly release for control.
Avian Flu
A lot of back and forth in the lay press about influenza A H5N1. My take on the bottom line is that there is nothing substantive that is new. I'm still watching closely for more concerning trends including extensive infection in pigs (where conversion to a strain with greater ability to infect humans is more of a risk) and any evidence of human-to-human transmission.
USDA monitoring is ongoing, with of course many infections in wild and domestic birds, cattle, and other mammals including a flurry of domestic cat infections recently. The map below is current as of February 26.
Our new agriculture secretary has released a plan for avian flu control. It is advertised as a means to lower egg prices which is fine, but we won't see any impact on that soon. I'm just glad we're seeing some movement to get a handle on this. The more H5N1 circulates in any animal, the more likely we'll see a new strain with greater potential to sicken humans.
In the meantime, I might try to steal my wife's oatmeal stash a few mornings a week.
Hooray for MMWR!
Not only does this week's edition look like the old days, it even included a sensitive topic for the current political administration: HPV vaccine.
HPV was strikingly effective in lowering the rate of cervical precancers in young women (the solid blue lines below) as well as in women in their late twenties. The fact that the current administration allowed them to publish these results is encouraging; HPV vaccine has been a target as well as a source of income (from lawsuits) for RFK Jr. in the past.
Last year's flu vaccine early estimates of effectiveness looked like a glass-half-empty versus -full in the lay press. The half-empty folks point to somewhat low effectiveness against all infections, but that's not the point. As with other respiratory virus vaccines, the main point of vaccination is preventing healthcare visits and serious outcomes. Here's the bottom line we should pay attention to: "Interim 2024–2025 seasonal influenza VE estimates were derived from four U.S. VE networks. Among children and adolescents, VE was 32%, 59%, and 60% in outpatient settings (three networks) and 63% and 78% against influenza-associated hospitalization (two networks). Among adults, VE was 36% and 54% in outpatient settings (two networks) and 41% and 55% against influenza-associated hospitalization (two networks)."
I'm in the half-full camp.
WRIS
I think we might really be headed down for winter respiratory infection season, largely due to a sustained decrease in influenza with no significant upswings in covid. RSV is almost out the door. Here's the latest from FluView.
That's not to say it's gone, however. We're definitely still in flu season in many areas of the country.
FDA Advisory Committees
I'm perplexed about why the FDA VRBPAC's scheduled meeting was cancelled. Supposedly the selection of next fall's flu vaccine composition will be done internally by the FDA, but one of the key advantages of the VRBPAC meetings was the chance for anyone, including the general public, to view the discussions in real time and get a better understanding of issues and risks/benefits.
I have a bit of personal experience to illuminate this. I've participated as a panel member on several FDA Advisory Committee meetings, though never anything to do with vaccines. Here are some key points that I can relate from first-hand experience.
I filled out an incredible number of forms about my potential conflicts of interest for every session. It was the equivalent of a paper strip search.
I spent many hours/days reviewing documents with a lot of raw data, both from FDA experts as well as from any pharmaceutical companies and device manufacturers. It was a very granular level of detail.
Every session included presentations by mostly lay public individuals given time to speak at the meeting. It was a broad representation: patients and relatives of patients who might benefit (or be harmed) by the product, other industry and association representatives, and yes, some pseudo-science/misinformation folks.
The discussion was very helpful; sometimes my mind changed as I learned from others.
All committee members explained their votes. The votes were not binding to the FDA, but I can't remember a situation where they didn't follow the vote for any of the committees I served on.
My exact recollection has faded, but I think at first I was reimbursed for lunch but later I wasn't. Everyone was reimbursed for travel and lodging when the meetings were held in person in the DC area. Of course, since I'm local that really didn't amount to much even if I submitted my gas mileage! In short, people serve on these committees for civic duty, not for any remuneration.
Now that meetings are virtual, there is not much reason to cancel them. The cost is born by the committee members; FDA and industry participants still need to do the same amount of work. I hope transparency in healthcare administration will return soon.
Paint It Black
This Stones' song came on my Pandora station just as I was wrapping up my first draft of this post. The sun isn't quite "blotted out from the sky" from the FDA VRBPAC and CDC ACIP postponements and cancellations, but it's enough to cast a shadow on my sunny day. Here's to brighter times.
The title above is one of several great turns of phrase in the book I just finished reading, Edith Wharton's Age of Innocence. It refers to an episode where the protagonist was at a loss for words during a poignant encounter and presumably only later thought of something better to have said. I've been there.
Next Round for Covid Vaccine
The FDA's Vaccine and Related Biological Products Advisory Committee finally had their meeting last week; it had been postponed to give a little more time to see which way the new SARS-CoV-2 variants were headed. I was able to listen in on most of the meeting and have reviewed all the documents. The vote was unanimous to choose a monovalent JN.1-based vaccine for the next iteration, no surprise and in agreement with the recent WHO decision I discussed recently. (For those interested, there is quite a bit of international collaboration on these types of decisions. See the ICMRA posting about covid vaccines.) Still, there were some interesting updates on covid in general. I'll try to distill this down into the main takeaways.
The Latest on Epidemiology (from Thornburg FDA presentation)
Current circulation of SARS-CoV-2 is relatively low. Although our reporting is not as reliable these days, looking just at percentage of positive covid tests in orange you can see we are in a lull now, though perhaps with a hint of an uptick. This is pretty similar to last summer when we saw a bit of a surge in summer into fall and winter. SARS-CoV-2 still has not come around to a winter seasonality seen with other coronaviruses of with influenza, making predictions for surges and vaccine composition very tough.
JN.1 lineages replaced XBB.1.5 lineages during winter 2023-2024. I like the depiction below because it's looking at normalized numbers of positive tests rather than a percentage of positive tests due to different variants. This gives a better appreciation of numbers of cases and shows that we are still talking about relatively low numbers compared to 2022.
Here's a closeup of the most recent part of the above slide showing that KP.2-like, KP.3, and other JN.1 derivatives are starting to take over, though still all at very low numbers.
The recent subvariants have very few differences from other JN.1-derived strains and antigenically are very similar. This has important meaning for vaccine choice - should it be the original JN.1 variant or one of these newer KP.2 or KP.3 type subvariants, currently at extremely low numbers? Look at the last 2 rows in the table below, showing that these newer subvariants have very few mutation differences from the earlier JN.1-like variants.
In a totally new and as yet unpublished CDC analysis, severity of JN.1 infections does not appear to be worse than earlier lineages. The trend was towards milder illness, though not statistically significantly different. Note these numbers are just for adults.
Vaccine Effectiveness in Children (from Link-Gelles FDA presentation)
This it tough to estimate because children generally have milder disease, plus so few children are vaccinated. Adult data is pretty favorable for VE; SGT failure is a faster method of testing and correlates will with JN.1 lineage strains. 2023-2024 VE drops a little with these strains compared to effectiveness against XBB lineage strains.
On the pediatric side, it's important to remember that the vast majority of US children have been infected with SARS-CoV-2 at some time in their lives - this has been apparent since late 2022.
So, it's important to determine any VE now in light of prior infection and vaccination. We can't rely on older estimates. Here's the best and latest estimates for VE in children who received vaccine in the past year. Confidence intervals are relatively wide, reflecting the small numbers able to be studied, but do show benefit in prevention of ED or urgent care use. VE wanes with time after vaccination as it does with all age groups, but there is clear benefit for covid vaccination of children.
David Wentworth, representing WHO, delivered a wonderful explanation of the complexities in choosing among current subvariants for vaccine inclusion. He had this great quote: "... antigenic evolution just speeds up waning immunity." The variant evolution we're seeing now is parallel, i.e. lots of different subvariants evolving on their own, in parallel, rather than one subvariant evolving into another, and then into another, etc. Parallel evolution is what XBB lineages did previously, and we're seeing it now in the JN.1 groups. The slide below demonstrates this process with a timeline on the X axis.
The dilemma in choosing composition of the next vaccine is that no one knows which way the very new subvariants will evolve in terms of antigenic similarity to earlier JN.1 strains. Currently, KP.2, KP.3, and JN.1.23 are within what is thought to be close proximity to JN.1 in terms of antigenic similarity and therefore a vaccine based on any of those likely will have cross-reactivity with one another, enough to provide protection. However, as illustrated by the arrows, it just isn't known how the offspring of the newer subvariants will evolve - will it be farther away from JN.1 and each other, or will it remain relatively stable?
No one can predict what next fall's or winter's subvariants will look like. Once they appear, new lab testing would need to be done, ideally using human serum containing antibody to the newer strains, which Wentworth stated would take about a month to produce. So, it's not something that can be turned around quickly.
Also, it bears mentioning that virtually all of the immunity studies involve neutralizing antibody. Antibody does correlate well with VE, but T-cell immunity also is important. We don't see as much data about this arm of the immune system because the studies are more difficult.
All 3 US vaccine manufacturers, Moderna, Pfizer, and Novavax, presented their new data at the meeting. They are developing and testing new vaccines "at risk," meaning the companies are making vaccines without funding currently, risking their own research and development dollars, hoping whatever they are working on will be recommended for the next covid vaccine rounds and allow them to recoup their investment. Moderna and Pfizer have both developed JN.1- and KP.2-based mRNA vaccines. Novavax, the adjuvanted protein-based vaccine, only developed a JN.1-based vaccine. The protein vaccine takes much longer to construct than do mRNA vaccines, about 6 months to get good data in all. So, if a KP.2 or other vaccine were recommended, Novavax would need to start over and wouldn't be ready until about December.
I don't usually like to use pharma slides to illustrate points, but this one from Pfizer isn't biased in favor of their product and I think nicely shows the current situation, including how closely related the newer subvariants are to JN.1.
In the discussion after the vote to have a monovalent JN.1-based vaccine, which could mean one based on KP.2, the majority of the group felt that using the JN.1 variant rather than KP.2 or another subvariant was the best route, both to allow Novavax to be ready this fall but also not to take a chance that fall and winter predominant subvariants might be more antigenically removed from KP.2 antigenically. All in all I felt this was the right choice, though I probably wouldn't have let Novavax's problems affect the decision; very few US residents have received Novavax in the past, though it is nice to have an alternative to mRNA vaccines available.
On June 7 the FDA formally recommended sticking with the JN.1 strain for this next vaccine round. Next step with be the CDC's Advisory Council on Immunization Practices meeting the end of this month, where the official seal of approval will be issued. I'm sure Moderna, Pfizer, and Novavax already are ramping up production.
NASEM Long Covid Report Available
Long covid remains a quagmire, lots of different symptoms, many of which are vague, and still no definite light shed on diagnosis and treatment of what is likely a heterogenous group of conditions requiring different approaches. The National Academies of Science, Engineering, and Medicine published their full report, available free online. I haven't gotten through all of it, it's pretty long, but it is of interest to those practitioners who see these patients. Most of the evidence is from adults, but it appears that pediatric patients tend to have a better prognosis, especially if improvements are occurring in the first year after onset. Note that a positive covid test is not required for diagnosis testing may not have been done at the time of the triggering infection and antigen or PCR tests will have reverted to negative by the time a long covid diagnosis is considered.
Doxycycline for Post-Exposure Prophylaxis of STIs
The official guidelines appeared this past week, although the gist of the recommendations had been floated previously. Particularly high risk groups are gay, bisexual, and other men who have sex with men and transgender women. The summary is very helpful for practitioners who may want to print out and post Box 1 and Box 2 in their workspaces. Note that the recommendations apply just to those high risk groups.
Summer Bugs!
Bugs in the sense of both insects and microbes. We now have more details about a new rickettsial agent, termed species C6269, that caused a Rocky Mountain Spotted Fever-like illness in 2 individuals in northern California last summer. Both had severe disease, were hospitalized and treated with doxycycline, and survived. As always, keep RMSF and other tick-borne diseases in mind during our warm months.
Speaking of bugs, our dog came down with a skin abscess, expertly debrided by her veterinarian. She is now enjoying chewable amoxicillin/clavulanate but is less thrilled with her "cone of shame." The vet had another bug concern, however. She didn't want the dog to spend much time outside - apparently it is also maggot season, and they love open dog wounds. The vet doesn't know I'm an ID doctor, and I was trying to come up with some clever comment on maggots but failed at that moment - belated eloquence of the inarticulate!
Courtesy of Wikipedia. Hope you aren't eating as you read this.
Yesterday I made a trip (dare I say pilgrimage?) to my favorite neighborhood coffee place, a coffee roaster only open to the public on weekend mornings. It is tucked away in a small row of establishments mostly consisting of small business headquarters and tiny religious meeting places; not much going on except for the weekend coffee business. When things hit lockdown for the pandemic, the coffee started flowing again after the owner opened a window to the parking lot to make a walk up outdoor order site. I was happy to park and wait for my cappuccino and bag of beans.
I hadn't been there in a few weeks, and now the walkup window is closed. Inside, the already tiny seating area is even smaller with the counter in front of the main prep area shut down. I waited with a group of about 15 people, some masked, some not, and had a chance to catch up with Felix the owner. Looking around, I realized I was witnessing the future of the pandemic.
I didn't spend my wait there trying to read coffee grounds to predict the future, but as I said last week our current ability to predict the future is limited by poor data (less testing, home testing not reported, some states decreasing reporting frequency, etc). Tasseography might be as accurate as anything else. Looking to the UK once again for hints of the future, the reproductive number there is holding steady or maybe drifting down, a good sign. The variant situation is interesting, still with an overwhelming predominance of BA.2 but now with some newer recombinant lineages and even some totally new omicron sublineages (BA.4 and BA.5) detected last week. Nothing to panic about, just keep a watch.
A Befuddled FDA
Last Wednesday the FDA VRBPAC met to discuss the issue of vaccine boosters. I had a busy clinical load that day so could only attend the live meeting intermittently. Also, due to some technical problems, parts of the live meeting and the recording itself are missing audio input, including a key portion that I wanted to hear where members questioned Israeli scientists about 4th doses in older adults. The slides themselves are available though, and do provide a lot of information.
I don't think I've ever seen a group of medical experts struggle more with trying to blaze a path forward, entirely understandable because of the uncertainties of this pandemic particularly in predicting future variant emergence. What is clear, however, is that we need a new strategy available likely by the fall, when cold weather returns and people again move to more frequent indoor gatherings which will facilitate SARS-CoV-2 transmission like the Gridiron Dinner last week. Here are a few of my take-home messages from the meeting.
There isn't enough time to get clinical data on any new variant in time to decide on vaccine composition; if the past is any predictor, by the time the variant appears it's already too late for a variant-specific vaccine to be developed. This is totally different from seasonal influenza where strains seen at the end of the previous season can be reasonable guides for vaccine production for the next season. Things happen much more quickly with SARS-CoV-2. Also, at present and likely for the extended future, we don't have an antibody or other correlate of protection. Even if we did, that could change with the next variant as we've seen so clearly with omicron.
Future vaccines likely will need to bivalent or multivalent, covering more than one strain/variant, or perhaps a new approach targeting a conserved region of the virus like the nucleoprotein will be better. That latter strategy is underway but could take a longer time to develop. I doubt a vaccine targeting just the original omicron strain will cut the mustard for boosters next fall.
We've just witnessed a super spreader event in DC with some big names infected. Given current behaviors, it won't be just my favorite coffee shop that's risky. Each of us will need to weigh our own risk profiles, taking into account both individual risk factors for severe disease as well as risk factors of our close contacts. I interact with immunocompromised and unimmunized children all the time, I'll be playing it very much safe to protect them. I wear N95 masks full time when I'm around them and also when I'm in the grocery store or other indoor settings.
And yes, I wrote this post while sipping a nice cup of coffee made from Colombian beans: "medium body with hints of honey, pear, cardamom & fennel." No, I couldn't really pick out those flavors, but it tasted great.
I spent most of my day December 10 trying to catch as much of the FDA Center for Biologics Evaluation and Research (CBER) meeting of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) discussion of the Pfizer/BioNTech COVID-19 vaccine. Although I had some interruptions and much multi-tasking, I was able to watch most of the proceedings, plus I did have a chance to review the detailed briefings from FDA and Pfizer as well as all of the presentation slides, posted online for everyone. Overall I came away feeling that we now have a very clear picture of the data, certainly enough to make decisions about this vaccine for the short term. Obviously they covered a ton of information, but I'll try to distill down to the essentials.
First, the overview and major take-home messages. As you may already know, this is a messenger RNA vaccine; the technology and science for making these vaccines has been around for quite a while and been tested in small numbers of humans for different purposes. However, this is the first mRNA vaccine to undergo widespread testing and presumably use in people. The cartoon below is from the Pfizer slides and I think shows you how this works. The modified mRNA is contained in lipid nanoparticles (LNP) and when injected ends up in cells where the mRNA instructs the cell to make the SARS-CoV-2 spike protein. The protein then triggers an inflammatory response such that the recipient makes antibody to the protein as well as memory T and B cells, then lies in wait to attack anything possessing the spike protein to enter the body.
In terms of safety, bottom line is that no serious concerns were raised in the 20,000+ individuals who received the vaccine (the other half of the subjects received saline placebo injections). Local side effects such as pain and swelling at the injection site occurred but nothing dramatic there. Systemic reactions like fatigue and chills were reported by a few percent of vaccine recipients; fever also occurred and usually of short duration. Side effects were more common after the second vaccine dose. Efficacy was as you have heard in news reports, in the mid-90s% range and much higher than I had hoped originally.
Now for the nuances and special populations. You've probably heard about the 2 vaccine recipients in England who may have experienced severe allergic reactions to the vaccine. Pfizer presented what little is known so far about this, and the best I can say is that it is still pretty murky. It didn't really sound like true anaphylaxis to me, but we'll just need to wait for more details, I'm hoping in the next few days. The current trial did not include individuals with severe allergy profiles, unlike the 2 British recipients this week.
A couple other caveats from the safety aspect. Regional lymphadenopathy occurred in 64 individuals in the vaccine group versus 6 in the control group, nothing worrisome but certainly plausible as an uncommon side effect. Bell's palsy occurred in 4 vaccine recipients versus none of the controls, but that level is within the rate of Bell's palsy that would be expected in the general population not receiving any vaccine, so difficult to know if any connection to the Pfizer vaccine.
The immune response to this vaccine is what is termed "Th-1 biased." That's a good thing, because in the past (e.g. an RSV vaccine trial in the 1970s), vaccines have the capability to produce an exaggerated immune response by the host when exposed to the virus. The immunology of that process is now understood, and a Th-1 biased immune profile protects against this. The few vaccine recipients in the Pfizer trial who did develop subsequent infection with SARS-CoV-2 did not show evidence of severe disease; in fact it was very mild.
In terms of special populations, the trial did not enroll immunocompromised individuals though this is planned for the future. They might need a different vaccine dose; this will take a while to figure out. Similarly, pregnant women were not enrolled. However, 23 women subsequently became pregnant, 12 in the vaccine group and 11 in the placebo group. The only known outcome so far is 2 women in the placebo group experienced a spontaneous abortion. The remainder of the pregnancies are still ongoing so we'll hear more about that later. In the meantime, the language of what to do about guidance for pregnant women will come from the FDA. My guess, and it's only that, is pregnancy will not be an absolute contraindication to vaccination and women will be directed to discuss individually with their physician to weigh benefits versus potential risks. In terms of racial and ethnic distribution, the study group included a little under 10% Black or African Americans (about 4000 total) and a little over 25% Hispanic/Latinx participants.
The final special group, the one this audience cares most about, is children. The bulk of the study participants were adults 18 years and older, with a small number of 16- and 17-year olds. Pfizer has begun enrolling younger subjects down to age 12 years, a total of 2000, but no data on that yet. If no problems in that population, they will move to the 5-11 year-old age group, perhaps around April 2021, but they may need to determine if vaccine dose should be different in this younger population. I was surprised that there was some hesitancy from VRBPAC voting members about recommending use of the vaccine for the 16-17 year age group but ultimately the panel voted to recommend authorizing the vaccine for ages 16 and older, with 17 votes in favor, 4 against, and 1 abstention.
Two other important caveats from the FDA meeting: first, extensive post-authorization tracking is planned and already in place. This is called pharmacovigilance and will use both existing and newer vaccine tracking measures. I am very reassured about the quality of this pharmacovigilance plan, and this is where we begin to get some idea of how long immunity from the vaccine will persist. Second is the tricky ethical issue of what to do about the placebo recipients from this trial. Should they all be offered vaccines, which would make some of the long-term follow-up more difficult to assess? It would be great to invite all the trial participants to participate in a "blind crossover" trial, where prior vaccine recipients receive 2 doses of placebo and prior placebo recipients get 2 doses of the vaccine, everyone still remaining blinded but now everyone has the benefit from the vaccine. However, the logistic difficulties of performing what is essentially a new clinical trial for 40,000+ people is significant.
Next steps for this vaccine include what we hope will be a statement the evening of December 11 from FDA regarding recommendation for emergency use authorization. ACIP/CDC meetings are scheduled the afternoons of December 11 and 13, culminating in a vote to decide on whether the data warrant a recommendation for going forward assuming FDA recommends authorization. Then, on December 17, FDA VRBPAC will meet to discuss the Moderna vaccine data, with meeting materials to be posted soon on the web link earlier in this post.
In closing, I need to answer the many questions I've received from friends and colleagues: if offered, will I choose to receive this vaccine? My answer is unquestionably yes. Although we don't have long-term follow up of recipients, most significant side effects from vaccines appear in the first 6 weeks after immunization, and we have lots of information about that time period. Of course we don't know about any extremely rare side effects, but we never have that information about new drugs or vaccines until they are in widespread use. I'm perhaps a bit biased ahead of time in favor of vaccination: my age and occupation puts me in a high-risk group, I'm very familiar with the FDA review process and know several of the reviewers (no, I don't have any inside information about what they are doing with this or any other vaccine), and it turns out one of the senior vice presidents at Pfizer who presented most of the clinical data is an old friend of mine. I don't think any of these potential biases is coloring my decision, however.
